Time Course of Changes in Peripheral Blood Gene Expression During Medication Treatment for Major Depressive Disorder.

Changes in gene expression (GE) during antidepressant treatment may increase understanding of the action of antidepressant medications and serve as biomarkers of efficacy. GE changes in peripheral blood are desirable because they can be assessed easily on multiple occasions during treatment. We report here on GE changes in 68 individuals who were treated for 8 weeks with either escitalopram alone, or escitalopram followed by bupropion. GE changes were assessed after 1, 2, and 8 weeks of treatment, with significant changes observed in 156, 121, and 585 peripheral blood gene transcripts, respectively. Thirty-one transcript changes were shared between the 1- and 8-week time points (seven upregulated, 24 downregulated). Differences were detected between the escitalopram- and bupropion-treated subjects, although there was no significant association between GE changes and clinical outcome. A subset of 18 genes overlapped with those previously identified as differentially expressed in subjects with MDD compared with healthy control subjects. There was statistically significant overlap between genes differentially expressed in the current and previous studies, with 10 genes overlapping in at least two previous studies. There was no enrichment for genes overexpressed in nervous system cell types, but there was a trend toward enrichment for genes in the WNT/β-catenin pathway in the anterior thalamus; three genes in this pathway showed differential expression in the present and in three previous studies. Our dataset and other similar studies will provide an important source of information about potential biomarkers of recovery and for potential dysregulation of GE in MDD

Origin and significance of 'dispersed facies' basal ice: Svínafellsjökull, Iceland

Dispersed facies basal ice - massive (i.e. structureless) ice with dispersed debris aggregates - is present at the margins of many glaciers and, as a product of internal glacial processes, has the potential to provide important information about the mechanisms of glacier flow and the nature of the subglacial environment. The origin of dispersed facies is poorly understood, with several hypotheses having been advanced for its formation, and there is disagreement as to whether it is largely a sedimentary or a tectonic feature. We test these established hypotheses at the temperate glacier Svfnafellsjokull, Iceland, and find that none fully account for dispersed facies characteristics at this location. Instead, dispersed facies physical, sedimentological and stable-isotope (5180, 8D) characteristics favour a predominantly tectonic origin that we suggest comprises the regelation and straininduced metamorphism of debris-rich basal ice that has been entrained into an englacial position by tectonic processes operating at the base of an icefall. Further thickening of the resultant dispersed facies may also occur tectonically as a result of ice flow against the reverse bed slope of a terminal overdeepening. Lack of efficient subglacial drainage in the region of the overdeepening may limit basal melting and thus favour basal ice preservation, including the preservation of dispersed facies. Despite the relatively low sediment content of dispersed facies (~1.6% by volume), its thickness (up to 25 m) and ubiquity at Svfnafellsjokull results in a significant contribution to annual sediment discharge (1635-3270 m3 a"1) that is ~6.5 times that contributed by debris-rich stratified facies basal ice

Large Magellanic Cloud Microlensing Optical Depth with Imperfect Event Selection

I present a new analysis of the MACHO Project 5.7 year Large Magellanic Cloud (LMC) microlensing data set that incorporates the effects of contamination of the microlensing event sample by variable stars. Photometric monitoring of MACHO LMC microlensing event candidates by the EROS and OGLE groups has revealed that one of these events is likely to be a variable star, while additional data has confirmed that many of the other events are very likely to be microlensing. This additional data on the nature of the MACHO microlensing candidates is incorporated into a simple likelihood analysis to derive a probability distribution for the number of MACHO microlens candidates that are true microlensing events. This analysis shows that 10-12 of the 13 events that passed the MACHO selection criteria are likely to be microlensing events, with the other 1-3 being variable stars. This likelihood analysis is also used to show that the main conclusions of the MACHO LMC analysis are unchanged by the variable star contamination. The microlensing optical depth toward the LMC is = 1.0 +/- 0.3 * 10^{-7}. If this is due to microlensing by known stellar populations, plus an additional population of lens objects in the Galactic halo, then the new halo population would account for 16% of the mass of a standard Galactic halo. The MACHO detection exceeds the expected background of 2 events expected from ordinary stars in standard models of the Milky Way and LMC at the 99.98% confidence level. The background prediction is increased to 3 events if maximal disk models are assumed for both the MilkyWay and LMC, but this model fails to account for the full signal seen by MACHO at the 99.8% confidence level.Comment: 20 pages, 2 postscript figues, accepted by Ap

Physical assault in the previous year and total and cause-specific mortality in Russia: a case-control study of men aged 25-54 years.

Background: Violence has important health effects. The results of exposure to physical violence include, but may not be limited to, death from suicide and homicide. The connection between the experience of assault and risk of death from causes other than homicide and suicide has rarely been examined. Methods: We analysed data from the first Izhevsk Family Study (IFS-1), a population-based case-control study of premature mortality in Russian men. Structural equation models were used to obtain odds ratios (ORs) for the association between the proxy report of physical attack in the previous year and mortality. Results: The estimate of the all-cause mortality OR for assault, after adjusting for alcohol use and socio-demographic confounders, was 1.96 (95% confidence interval: 1.71, 3.31). Strong cause-specific associations were found for external causes, but associations were also found for deaths from cardiovascular and alcohol-related deaths. Conclusions: We found that, in our population of working-aged Russian men, there was a strong association between physical assault and mortality from a wide range of causes. Other than direct effects of physical assault on mortality, residual confounding is an important possibility. The association between assault and mortality, particularly from cardiovascular and alcohol-related causes requires replication and further investigation

Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder.

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS.MethodsMedications were tabulated for 181 MDD patients who underwent a six-week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left-sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS-SR30) total score after 2, 4, and 6 weeks.ResultsUse of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non-users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non-users (39.2% vs. 22.0%, p = 0.02).ConclusionsConcomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis-based treatment studies will aid in determining causal relationships between medication treatments and outcome

Development and Persistence of 'Static' or 'Dead' Zones in Flows

Certain ceramic products are formed through extrusion processes, where a slurry is forced through small openings to form such products as filters. At the top is a large tank. The slurry is forced through the tank into an extrusion chamber, and then out through slots to form the finished product. [The slurry may be thought of as a mixture of clay (or other polymers), water, and other binders. There are many ways to model this mixture, some of which will be discussed in this report. For instance, the slurry can be modeled as a non-Newtonian fluid, a two-phase flow with liquid and solids, or a viscoelastic fluid. One can also model the mixture as an elongated particle suspension in water, where changes in the orientation of the particles could affect the flow.] After the extrusion process is complete, one finds that ‘dead zones’ of dry paste accumulate in two areas. Most prominently, they occur at the lower corners of the tank. They also occur on the floor of the extrusion chamber near the slots, both near and away from the walls. Since we will consider wall effects in the tank, for the extrusion chamber we consider only flow cells sufficiently far away from the walls. Then we may exploit the periodic nature of the device and consider only a single flow cell. The aim of this project is to determine the formation mechanisms of these dead zones, and see how they affect the overall flow

A Study of Two Dwarf Irregular Galaxies with Asymmetrical Star Formation Distributions

Two dwarf irregular galaxies, DDO 187 and NGC 3738, exhibit a striking pattern of star formation: intense star formation is taking place in a large region occupying roughly half of the inner part of the optical galaxy. We use data on the H i distribution and kinematics and stellar images and colors to examine the properties of the environment in the high star formation rate (HSF) halves of the galaxies in comparison with the low star formation rate halves. We find that the pressure and gas density are higher on the HSF sides by 30%–70%. In addition we find in both galaxies that the H i velocity fields exhibit significant deviations from ordered rotation and there are large regions of high-velocity dispersion and multiple velocity components in the gas beyond the inner regions of the galaxies. The conditions in the HSF regions are likely the result of large-scale external processes affecting the internal environment of the galaxies and enabling the current star formation there

A Comparison of Young Star Properties with Local Galactic Environment for LEGUS/LITTLE THINGS Dwarf Irregular Galaxies

We have explored the role environmental factors play in determining characteristics of young stellar objects in nearby dwarf irregular and blue compact dwarf galaxies. Star clusters are characterized by concentrations, masses, and formation rates; OB associations by mass and mass surface density; O stars by their numbers and near-ultraviolet absolute magnitudes; and H ii regions by Hα surface brightnesses. These characteristics are compared to surrounding galactic pressure, stellar mass density, H i surface density, and star formation rate (SFR) surface density. We find no trend of cluster characteristics with environmental properties, implying that larger-scale effects are more important in determining cluster characteristics or that rapid dynamical evolution erases any memory of the initial conditions. On the other hand, the most massive OB associations are found at higher pressure and H i surface density, and there is a trend of higher H ii region Hα surface brightness with higher pressure, suggesting that a higher concentration of massive stars and gas is found preferentially in regions of higher pressure. At low pressures we find massive stars but not bound clusters and OB associations. We do not find evidence for an increase of cluster formation efficiency as a function of SFR density. However, there is an increase in the ratio of the number of clusters to the number of O stars with increasing pressure, perhaps reflecting an increase in clustering properties with SFR